title: Phase 2 trial of a novel capecitabine dosing schedule in combination with bevacizumab for patients with metastatic breast cancer.
abstract: BACKGROUND
  Capecitabine has antitumor activity in metastatic breast cancer (MBC); however, its optimal dose and schedule remain unclear. Mathematical modeling predicts that a capecitabine schedule 7 days of treatment followed by 7 days of rest (7-7) will improve efficacy and minimize toxicity. Bevacizumab has demonstrated the ability to improve outcomes when it is added to chemotherapy, including capecitabine, in the first-line and second-line settings.
  
  
  METHODS
  Patients with measurable MBC received oral capecitabine (2000 mg twice daily; 7-7), and intravenous bevacizumab (10 mg/kg every 2 weeks). The primary endpoint was the response rate. Secondary endpoints included toxicity, the clinical benefit rate, and progression-free survival (PFS).
  
  
  RESULTS
  Forty-one patients were treated. After a median of 7 cycles (range, 1-32 cycles), partial responses were observed in 20% of patients, and stable disease for ≥6 months was noted in 35% patients. The median PFS was 8 months. The most common treatment-related toxicities were hand-foot syndrome (49% grade 2, 20% grade 3/4) hypertension (12% grade 2, 10% grade 3/4), and fatigue (12% grade 2, 2% grade 3/4). Diarrhea (5% grade 2, 0% grade 3/4), nausea (0% grade 2-4), and vomiting (0% grade 2-4) were rare.
  
  
  CONCLUSIONS
  Capecitabine administered for 7 days followed by a 7-day rest in combination with bevacizumab had modest efficacy and an acceptable toxicity profile in patients with MBC. Gastrointestinal toxicity with this schedule was minimal.
authors.affiliation: Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Devika
authors.initials: D
authors.lastname: Gajria
authors.forename: Kim
authors.initials: K
authors.lastname: Feigin
authors.forename: Lee K
authors.initials: LK
authors.lastname: Tan
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.forename: Stephanie
authors.initials: S
authors.lastname: Geneus
authors.forename: Maria
authors.initials: M
authors.lastname: Theodoulou
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Traina
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil